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Objective(s): In developing countries, including Iran, premature mortality imposes a significant economic burden on these countries through lost productivity. Accordingly, this study tried to calculate the economic consequences of premature deaths caused by the main causes of death in Iran in 2021. Methods: This was a cross-sectional, quantitative and analytical study that was conducted using secondary data. For data analysis, all deaths in Iran were considered according to age, gender and cause of death in 2021. The data used in this research was taken from the Global Burden of Disease Study. This study has followed the quantification of the economic burden of the main causes of premature death in Iran using the human capital approach. Results: The economic cost of premature death in Iran in 2021 accounted for about 1% of the GDP. The results of the research indicated a high contribution of men in the lost productivity in Iran, and also according to the time period studied in this research, the covid-19 disease had a great impact on premature mortality and increased lost productivity of the active population of Iran. Among other noteworthy results of this study was the economic cost of deaths caused by traffic accidents that target the young group of the population. The age group of 35 to 39 years had the largest share of lost productivity due to this cause, and these accidents accounted for 10% of the economic costs of premature death in men. Conclusion: The findings of this study suggest that sufficient resources should be allocated for healthcare and treatment and investment should be made in preventive and primary care in order to prevent avoidable deaths through treatment and prevention.